The Response of Alpha‐Aminoadipic Acid (2‐AAA) to Short Term Lysine Ingestion in Healthy Individuals
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT Background Higher circulating levels of the metabolite alpha‐aminoadipic acid (2‐AAA) associate with increased risk of diabetes and cardiometabolic disease. 2‐AAA is metabolised from lysine, an essential dietary amino acid. However, the effects of lysine intake on plasma levels of 2‐AAA were unclear. We measured post‐prandial changes in plasma and urine levels of 2‐AAA in healthy individuals in response to oral intake of 13 C isotope‐labelled lysine and assessed relationships with markers of glucose homeostasis. Methods We recruited healthy individuals ( N = 16) to an acute lysine challenge. We administered 5 g of 13 C Lysine‐HCL in 50 mL water as an oral bolus. We measured the appearance of 13 C lysine and 13 C 2‐AAA in plasma and urine over a period of 6 h post‐ingestion and assessed changes in insulin, C‐peptide, glucagon, and GLP‐1. Results We found that 13 C lysine and 13 C 2‐AAA were detectable in plasma 30 min post‐ingestion, peaking on average 2 h post‐ingestion. Interestingly, non‐labelled lysine and non‐labelled 2‐AAA also increased. Individuals with higher plasma levels of 13 C 2‐AAA post‐ingestion also had higher levels of 13 C 2‐AAA in urine. The rate of appearance of 2‐AAA in plasma and excretion in urine differed between individuals and was associated with differences in waist‐to‐hip ratio (WHR). We observed increases in plasma insulin, C‐peptide, glucagon, and GLP‐1 post‐lysine ingestion. Conclusion Our data suggest that orally ingested lysine is catabolised to 2‐AAA over several hours. However, lysine ingestion also stimulates an increase in 2‐AAA from endogenous sources. The rate of production and excretion differs between individuals, suggestive of controlled regulation of this metabolic pathway. Individuals with a higher WHR, indicative of greater visceral adiposity, may have increased excretion of 2‐AAA, tryptophan, and kynurenine.
DOI: 10.1002/edm2.70168
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,280
Funders: American Heart Association, Vanderbilt University, Vanderbilt Institute for Clinical and Translational Research, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G2537422520, G2615776415, G2635992203, G3272238124, G364208108, Determinants of alpha-aminoadipic acid (2-AAA) and relationship to diabetes, G5679716143, Investigation of alpha-aminoadipic acid (2-AAA) as a novel modulator of the liver-pancreas axis, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G9000054231, G95160140
OpenAlex ID: W7130863243